A typical magnetization transfer (MT) phenomenon in biological tissues is caused by the interaction between the solid-like, macromolecular bound water protons, such as those in protein matrices and cell membranes, and the free bulk water. In most disease conditions, such as Multiple Sclerosis (MS), tumor, stroke, and fibrosis, the concentration of a bound water pool associated with proteins and lipids (such as myelin in MS) changes. MT ratio (MTR) imaging, defined as the ratio of water magnetic resonance imaging (MRI) images with and without off-resonance radiofrequency (RF) irradiation at a single frequency, has been used as a contrast mechanism to probe white matter diseases in brain. Typically, the offset frequency chosen for MTR imaging is rather large (>20 ppm) to avoid direct water saturation (DS) effects.
In biological tissues, the conventional magnetization transfer (CMT) effect from macromolecules is asymmetric with respect to water resonance and this MT asymmetry also interferes with Chemical Exchange Saturation Transfer (CEST) effects from other brain metabolites and macromolecules with exchangeable —OH, —NH and —NH2 protons. CEST contrast is either reduced or in some cases completely suppressed by MT asymmetry (MTasy) contamination.
Studies have been carried out to model the CMT effect along with DS using a two and three pool model. For example, see Morrison and Henkelman, “A model for magnetization transfer in tissue,” Magn. Reson. Med. 1996; Vol. 35, p. 277, and Henkelman, Stanisz, and Graham, “Magnetization transfer in MRI: a review,” NMR Biomed., 2001, Vol. 14, pp. 57-64. However, independent observation of the CMT spectrum has not been possible due to DS of the free water pool during z-spectra acquisition. Contamination of MT asymmetry to CEST has been reported by Hua and Jones in “Quantitative description of the asymmetry in magnetization transfer effects around the water resonance in the human brain,” Magn. Reson. Med., 2007, Vo. 58(4), pp. 786-793. However, to the inventors' knowledge, no successful studies have been published for removing MT asymmetry contamination.
A clear dip in z-spectra data centered at approximately −3.5 ppm, with respect to water proton resonance, has been reported, particularly at high field and is characterized as a magnetization exchange/nuclear Over Hauser effect (NOE) from aliphatic protons associated with labile proteins, peptides and lipids. Hereafter this effect is named as novel magnetization transfer (NMT) effect. To the best of the inventors' knowledge, there is no study exploring the NMT effect as an in-vivo contrast, probably due to contaminations from DS and MT effects. The NMT effect may provide unique image contrast that is different from CMT or any traditional contrast observed in MRI, and may serve as a specific marker for pathological changes in various diseases. However, removal of the dominant DS and CMT asymmetry contribution from NMT effects is crucial before their application to explore in-vivo tissue environment and changes related to disease conditions.